The broad aims of the proposed investigation are to study the effects of alcohol on the cellular membranes of the central nervous system and to clarify the biochemical mechanism associated with tolerance and physical dependence developed after long-term alcohol intake. Specifically, the study will: 1) examine the effects of alcohol on the membrane-dependent active transport processes related to neuronal activity in the central nervous system, 2) study the effects of long-term ethanol ingestion on the chemical composition and function of the neuronal membranes, and 3) evaluate the effects of chronic ethanol administration on some critical enzyme systems involved in the synthesis of putative neurotransmitters. Synaptosomal particles will be isolated from cerebral cortex and brain stem of squirrel monkeys (Saimiri sciureus) by sucrose density gradient centrifugation. The active uptake of biogenic amines (norepinephrine, serotonin and GABA) and active transport of choline by isolated synaptosomal particles will be examined in control and alcohol treated samples. Possible alcohol-membrane interaction in CNS will be evaluated by kinetic studies of both in vitro and in vivo systems. Enzyme levels of choline acetyltransferase, tyrosine hydroxylase and tryptophan hydroxylase will be assayed in cortical and subcortical regions of brain of control and experimental animal subjects addicted to alcohol. In addition, the activity of Na-K ATPase and the chemical composition of the synaptosomal membranes will be measured in control animals and animals subjected to long-term alcohol ingestion. BIBLIOGRAPHIC REFERENCES: Sun, A.Y. and Samorajski, T. (1975) The effects of age and alcohol on (Na plus K)-ATPase activity of whole homogenate and synaptosomes prepared from mouse and human brain. J. Neurochem. 24:161-164. Sun, A.Y. (1975) Alcohol-membrane interaction. I. Reversibility. Ann. NY Acad. Sci.